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首页> 外文期刊>Toxicology in vitro: an international journal published in association with BIBRA >Evaluation of a proposed in vitro test strategy using neuronal and non-neuronal cell systems for detecting neurotoxicity.
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Evaluation of a proposed in vitro test strategy using neuronal and non-neuronal cell systems for detecting neurotoxicity.

机译：使用神经元和非神经元细胞系统检测神经毒性的拟议体外测试策略的评估。

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摘要

The European Commission White Paper, "Strategy for a future chemicals policy" (EC, 2001) is estimated to require the testing of approximately 30,000 "existing" chemicals by 2012. Recommended in vitro tests require validation. As the White Paper (EC, 2001) requires neurotoxic data, this study evaluated an in vitro testing strategy for predicting in vivo neurotoxicity. The sensitivities of differentiated PC12 cells and primary cerebellum granule cells (CGC) were compared to undifferentiated PC12 cells which can indicate basal cytotoxicity. Cytotoxicants and neurotoxicants selected for testing covered a range of mechanisms and potencies. Neurotoxicants were not distinguished from cytotoxicants despite significantly different cell system responses using all endpoints; cell viability/activity, ATP depletion, MMP depolarisation, ROS production and cytoskeleton modifications. For all chemicals tested, neuronal-like cell systems were generally less sensitive than undifferentiated PC12 cells. Acute oral rodent LD(50) values correlated with cytotoxicity IC(50) values for the respective chemicals tested in each cell system. This study concluded that although simple non-specific assays are required to distinguish basal cytotoxicity from specific neurotoxicity by using different cell systems with different states of neuronal differentiation, further work is required to determine suitable combinations of cell systems and endpoints capable of distinguishing neurotoxicants from cytotoxicants.
机译：欧盟委员会的白皮书“未来化学品政策策略”（EC，2001年）估计需要在2012年前对大约30,000种“现有”化学品进行测试。建议的体外测试需要验证。由于白皮书（EC，2001）需要神经毒性数据，因此本研究评估了预测体内神经毒性的体外测试策略。将分化的PC12细胞和原代小脑颗粒细胞（CGC）的敏感性与未分化的PC12细胞进行了比较，这可以表明基础细胞毒性。选择用于测试的细胞毒物和神经毒物涵盖了多种机制和效力。尽管使用所有终点的细胞系统反应差异显着，但神经毒性和细胞毒性没有区别。细胞活力/活性，ATP耗竭，MMP去极化，ROS产生和细胞骨架修饰。对于所有经过测试的化学药品，神经元样细胞系统通常比未分化的PC12细胞敏感。急性口服啮齿动物的LD（50）值与每个细胞系统中测试的各种化学品的细胞毒性IC（50）值相关。这项研究得出结论，尽管通过使用具有不同神经元分化状态的不同细胞系统，需要简单的非特异性测定来区分基础细胞毒性和特异性神经毒性，但仍需要进一步的工作来确定能够区分神经毒性和细胞毒性的细胞系统和终点的合适组合。

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